[Treatment strategies for low-risk polycythemia vera].

Treatment selection for patients with polycythemia vera (PV) is based on patient age and history of thrombosis. The standard treatment is low-dose aspirin and phlebotomy for low-risk PV, with cytoreductive therapy added for high-risk PV. Thrombotic events and disease progression due to PV clone expansion affect the prognosis of PV. Although phlebotomy is effective in controlling hematocrit level, it has no effect on disease progression or PV-related symptoms. In Western countries, interferon (IFN) has been used as a cytoreductive therapy for PV. Long-term IFN therapy has been shown to result in sustained hematologic remission and molecular responses. Ropeginterferon-α-2b (ropeg-IFN), which is administered every two weeks, has recently become available. Clinical trials in patients with PV have shown that ropeg-IFN treatment is safe and efficacious, reducing JAK2V617F allele burden. Ropeg-IFN could ultimately affect long-term hematologic remission and molecular response in younger patients with low-risk PV, and may even offer a cure.

Paradoxical generator impedance behavior during catheter ablation in a patient with severe polycythemia.

An extremely high generator impedance in the blood pool can be observed in a patient with severe polycythemia. However, ablation can be performed safely as long as the generator impedance during contact with the myocardial tissue is within acceptable limits.

Top Ten Tips Palliative Care Clinicians Should Know About Caring for Patients with Myeloproliferative Neoplasms.

Myeloproliferative neoplasms (MPNs) are a group of rare chronic progressive blood cancers that vary widely in clinical presentation, yet all patients have a risk of disease progression and thrombotic complications. Diseases include primary myelofibrosis, polycythemia vera, and essential thrombocythemia. With current treatment approaches, most patients live a prolonged life, but many experience a complex of symptoms that negatively influence their functional status and quality of life. Although significant advances have been made in preventing arterial and venous complications while mitigating inflammatory processes, comprehensive palliative care can help address unmet complex physical and psychosocial needs on a long-term basis. This article, created by a multidisciplinary group of providers, offers an overview of MPNs so palliative care clinicians can better support patients with these hematologic cancers.

Miliary TB and COVID-19 Coinfection in a Patient With a History of Post-polycythemia Vera Myelofibrosis Treated With Ruxolitinib: A Case Report.

The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the diagnosis and management of tuberculosis (TB), a major public health issue. This case report discusses a 70-year-old female with post-polycythemia vera myelofibrosis (post-PV MF) treated with ruxolitinib who developed miliary TB amidst a COVID-19 infection. The patient presented with a flu-like syndrome over the past week with fatigue and weight loss the last month. When she was admitted to the hospital, the real-time polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was positive. Despite the typical COVID-19 presentation, her clinical and radiographic features raised suspicion for disseminated TB. Diagnostic tests, including bronchoscopy and PCR for Mycobacterium tuberculosis, confirmed miliary TB. She was treated with a standard antitubercular regimen, leading to symptomatic improvement. The interplay between COVID-19 and TB is complex, with COVID-19-induced immunosuppression, particularly lymphocytopenia, facilitating TB reactivation. Additionally, ruxolitinib, a Janus kinase (JAK) inhibitor used for myelofibrosis, impairs immune defense mechanisms, increasing infection risk, including TB. Prompt and accurate diagnosis of TB in the context of COVID-19 is crucial for effective management and improved patient outcomes. Clinicians should remain vigilant for TB reactivation in patients undergoing treatments such as ruxolitinib and consider alternative diagnoses despite positive SARS-CoV-2 tests. This report highlights the necessity for a comprehensive evaluation and timely intervention to mitigate the compounded risks of COVID-19 and TB.

An Unusual Case of Extramedullary Hematopoiesis in the Right Kidney.

Extramedullary hematopoiesis (EMH) is the formation of blood cells outside the bone marrow, typically occurring in response to chronic anemia or bone marrow dysfunction. While EMH is most commonly observed in the liver, spleen, and lymph nodes, its occurrence in the kidney is exceedingly rare. In this case report, we are presenting a case of a 49-year-old male diagnosed with polycythemia vera who had an incidental right renal mass, which was histo-pathologically proven as extramedullary hematopoiesis in the right kidney mimicking lymphoma. This case underscores the importance of considering EMH in the differential diagnosis of renal masses, especially in patients with a history of myeloproliferative disorders. Early recognition and appropriate management are crucial to avoid unnecessary interventions and manage the underlying hematological condition effectively. Accurate diagnosis through histopathological examination is crucial to avoid unnecessary surgical interventions.

Establishment of a nomogram model for predicting therapy complications in patients with polycythemia and deep venous thrombosis.

BACKGROUND: Patients with deep venous thrombosis (DVT) residing at high altitudes can only rely on anticoagulation therapy, missing the optimal window for surgery or thrombolysis. Concurrently, under these conditions, patient outcomes can be easily complicated by high-altitude polycythemia (HAPC), which increases the difficulty of treatment and the risk of recurrent thrombosis. To prevent reaching this point, effective screening and targeted interventions are crucial. Thus, this study analyzes and provides a reference for the clinical prediction of thrombosis recurrence in patients with lower-extremity DVT combined with HAPC. AIM: To apply the nomogram model in the evaluation of complications in patients with HAPC and DVT who underwent anticoagulation therapy. METHODS: A total of 123 patients with HAPC complicated by lower-extremity DVT were followed up for 6-12 months and divided into recurrence and non-recurrence groups according to whether they experienced recurrence of lower-extremity DVT. Clinical data and laboratory indices were compared between the groups to determine the influencing factors of thrombosis recurrence in patients with lower-extremity DVT and HAPC. This study aimed to establish and verify the value of a nomogram model for predicting the risk of thrombus recurrence. RESULTS: Logistic regression analysis showed that age, immobilization during follow-up, medication compliance, compliance with wearing elastic stockings, and peripheral blood D-dimer and fibrin degradation product levels were indepen-dent risk factors for thrombosis recurrence in patients with HAPC complicated by DVT. A Hosmer-Lemeshow goodness-of-fit test demonstrated that the nomogram model established based on the results of multivariate logistic regression analysis was effective in predicting the risk of thrombosis recurrence in patients with lower-extremity DVT complicated by HAPC (χ 2 = 0.873; P > 0.05). The consistency index of the model was 0.802 (95%CI: 0.799-0.997), indicating its good accuracy and discrimination. CONCLUSION: The column chart model for the personalized prediction of thrombotic recurrence risk has good application value in predicting thrombotic recurrence in patients with lower-limb DVT combined with HAPC after discharge.

Regorafenib-related erythrocytosis in metastatic extra-gastrointestinal stromal tumor: a case report.

Introduction: Regorafenib is an oral multi-targeted tyrosine kinase inhibitor (TKI) indicated for the treatment of various tumor types, including metastatic gastrointestinal stromal tumors (GIST), as a third-line systemic therapy. Erythrocytosis, which is characterized by an increase in erythrocyte count, hemoglobin, and hematocrit levels, has been described as a side effect of some antiangiogenic TKIs but has never been associated with regorafenib administration. Case presentation: An extra-GIST was diagnosed in a 58-year-old woman after she underwent surgery to remove a pelvic mass. Three years later, systemic therapy with imatinib was started due to pelvic disease recurrence. However, after six months, due to disease progression, we prescribed sunitinib, which the patient received for four years. Regorafenib was initiated in June 2019, and after six months, we noted an increase in the erythrocytes' count and hemoglobin (Hb) levels. Given that the patient had clinical benefit and hematocrit was within normal range, we only monitored the blood cell count and continued to give regorafenib at the same dose. The drug was then stopped for over six weeks due to hospitalization for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and Hb levels returned to normal. Therefore, we decided to restart regorafenib at a lower dose. However, Hb levels rose again in conjunction with increased hematocrit, resulting in the need for multiple phlebotomies. We attempted to restart regorafenib every other day, but it was unsuccessful, so we stopped it permanently in May 2023, and all values returned to normal. Conclusion: Regorafenib may cause secondary erythrocytosis that could not be dose-related, as this case report suggests. Secondary erythrocytosis might be a marker of TKI efficacy, given the patient's prolonged clinical benefit during regorafenib treatment (48 months). In patients receiving regorafenib, monitoring blood count as well as any symptoms associated with erythrocytosis may be suggested.

Potential biomarkers and immune characteristics for polycythemia vera-related atherosclerosis using bulk RNA and single-cell RNA datasets: a combined comprehensive bioinformatics and machine learning analysis.

Background: Polycythemia vera (PV) is a myeloproliferative disease characterized by significantly higher hemoglobin levels and positivity for JAK2 mutation. Thrombosis is the main risk event of this disease. Atherosclerosis (AS) can markedly increase the risk of arterial thrombosis in patients with PV. The objectives of our study were to identify potential biomarkers for PV-related AS and to explore the molecular biological association between PV and AS. Methods: We extracted microarray datasets from the Gene Expression Omnibus (GEO) dataset for PV and AS. Common differentially expressed genes (CGs) were identified by differential expression analysis. Functional enrichment and protein-protein interaction (PPI) networks were constructed from the CG by random forest models using LASSO regression to identify pathogenic genes and their underlying processes in PV-related AS. The expression of potential biomarkers was validated using an external dataset. A diagnostic nomogram was constructed based on potential biomarkers to predict PV-related AS, and its diagnostic performance was assessed using ROC, calibration, and decision curve analyses. Subsequently, we used single-cell gene set enrichment analysis (GSEA) to analyze the immune signaling pathways associated with potential biomarkers. We also performed immune infiltration analysis of AS with "CIBERSORT" and calculated Pearson's correlation coefficients for potential biomarkers and infiltrating immune cells. Finally, we observed the expression of potential biomarkers in immune cells based on the single-cell RNA dataset. Results: Fifty-two CGs were identified based on the intersection between up-regulated and down-regulated genes in PV and AS. Most biological processes associated with CGs were cytokines and factors associated with chemotaxis of immune cells. The PPI analysis identified ten hub genes, and of these, CCR1 and MMP9 were selected as potential biomarkers with which to construct a diagnostic model using machine learning methods and external dataset validation. These biomarkers could regulate Toll-like signaling, NOD-like signaling, and chemokine signaling pathways associated with AS. Finally, we determined that these potential biomarkers had a strong correlation with macrophage M0 infiltration. Further, the potential biomarkers were highly expressed in macrophages from patients with AS. Conclusion: We identified two CGs (CCR1 and MMP9) as potential biomarkers for PV-related AS and established a diagnostic model based on them. These results may provide insight for future experimental studies for the diagnosis and treatment of PV-related AS.

The JAK1/JAK2 inhibitor ruxolitinib inhibits mediator release from human basophils and mast cells.

Introduction: The Janus kinase (JAK) family includes four cytoplasmic tyrosine kinases (JAK1, JAK2, JAK3, and TYK2) constitutively bound to several cytokine receptors. JAKs phosphorylate downstream signal transducers and activators of transcription (STAT). JAK-STAT5 pathways play a critical role in basophil and mast cell activation. Previous studies have demonstrated that inhibitors of JAK-STAT pathway blocked the activation of mast cells and basophils. Methods: In this study, we investigated the in vitro effects of ruxolitinib, a JAK1/2 inhibitor, on IgE- and IL-3-mediated release of mediators from human basophils, as well as substance P-induced mediator release from skin mast cells (HSMCs). Results: Ruxolitinib concentration-dependently inhibited IgE-mediated release of preformed (histamine) and de novo synthesized mediators (leukotriene C4) from human basophils. Ruxolitinib also inhibited anti-IgE- and IL-3-mediated cytokine (IL-4 and IL-13) release from basophils, as well as the secretion of preformed mediators (histamine, tryptase, and chymase) from substance P-activated HSMCs. Discussion: These results indicate that ruxolitinib, inhibiting the release of several mediators from human basophils and mast cells, is a potential candidate for the treatment of inflammatory disorders.

The evolving landscape of polycythemia vera therapies.

INTRODUCTION: The treatment landscape of polycythemia vera (PV) has seen major advancements within the last decade including approval of ruxolitinib in the second line setting after hydroxyurea, ropegylated interferon-α2b, and advanced clinical development of a novel class of agents called hepcidin mimetics. AREAS COVERED: We provide a comprehensive review of the evidence discussing the risk stratification, treatment indications, role and limitations of phlebotomy only approach and pivotal trials covering nuances related to the use of interferon-α (IFN-α), ruxolitinib, hepcidin mimetics, and upcoming investigational agents including HDAC and LSD1 inhibitors. EXPERT OPINION: The research paradigm in PV is slowly shifting from the sole focus on hematocrit control and moving toward disease modification. The discovery of hepcidin mimetics has come as a breakthrough in restoring iron homeostasis, achieving phlebotomy-independence and may lead to improved thrombosis-free survival with stricter hematocrit control. On the other hand, emerging data with IFN- α and ruxolitinib as well as combination of the two agents suggests the potential for achieving molecular remission in a subset of PV patients and long-term follow-up is awaited to validate the correlation of molecular responses with clinically relevant outcomes of progression-free and thrombosis-free survival.

A Rare Case of High-Altitude Polycythemia Complicated by Spontaneous Splenic Rupture.

Wang, Bowen, Mengjia Peng,, Liheng Jiang,, Fei Fang,, Juan Wang,, Yan Li,, Ruichen Zhao,, and Yuliang Wang,. A Rare Case of High-Altitude Polycythemia Complicated by Spontaneous Splenic Rupture. High Alt Med Biol. 25:247-250, 2024.-High-altitude polycythemia, a condition characterized by an increase in red blood cellRBC mass, can occur after prolonged exposure to high altitudes. While several studies have explored the complications associated with high-altitude polycythemia, there is currently no literature available on spontaneous spleen rupture caused by high-altitude polycythemia. Here, we reported a case of acute abdominal pain and hemodynamic instability in a 36-year-old male who had been residing at high altitude for 6 years, without any recent history of trauma. Computed tomography imaging revealed significant fluid accumulation in the abdomen, and a tear of the splenic capsule was identified during the following laparotomy. Subsequent evaluations confirmed the presence of polycythemia secondary to prolonged high-altitude exposure as the underlying etiology. This case served as an important reminder that high-altitude polycythemia could lead to serious complications, such as spontaneous spleen rupture. Clinicians should be aware of this potential complication and consider it in the differential diagnosis of patients presenting with abdominal pain and hemodynamic instability in this population.

Cardiovascular Risk in Philadelphia-Negative Myeloproliferative Neoplasms: Mechanisms and Implications-A Narrative Review.

Myeloproliferative neoplasms (MPNs), encompassing disorders like polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are characterized by clonal hematopoiesis without the Philadelphia chromosome. The JAK2 V617F mutation is prevalent in PV, ET, and PMF, while mutations in MPL and CALR also play significant roles. These conditions predispose patients to thrombotic events, with PMF exhibiting the lowest survival among MPNs. Chronic inflammation, driven by cytokine release from aberrant leukocytes and platelets, amplifies cardiovascular risk through various mechanisms, including atherosclerosis and vascular remodeling. Additionally, MPN-related complications like pulmonary hypertension and cardiac fibrosis contribute to cardiovascular morbidity and mortality. This review consolidates recent research on MPNs' cardiovascular implications, emphasizing thrombotic risk, chronic inflammation, and vascular stiffness. Understanding these associations is crucial for developing targeted therapies and improving outcomes in MPN patients.

Impact of Phlebotomy on Quality of Life in Low-Risk Polycythemia Vera.

Polycythemia vera is an indolent myeloproliferative disorder that predisposes patients to venous and arterial thrombosis and can transform into myelofibrosis and acute myeloid leukemia. Consistent phlebotomy prevents life-threatening cerebrovascular and coronary artery disease and prolongs survival in low-risk polycythemia vera (patients under 60 years without thrombosis). However, despite its effectiveness in preventing serious complications, phlebotomy does not necessarily enhance the quality of life (QoL). This review assesses QoL issues associated with low-risk PV, explores alternative management strategies such as erythrocytapheresis, and discusses the roles of hydroxyurea, peginterferon, ruxolitinib, and other novel agents in potentially improving disease management and patient outcomes.

Case report: Woven-like coronary arteries in a patient with polycythemia vera.

BACKGROUND: Woven coronary artery (WCA) is a rare and underdiagnosed congenital anomaly that involves multiple thin and tortuous epicardial arterial conduits reassembling distally into a single lumen. Recanalized thrombus may present as woven-like coronary arteries, appearing similar to WCA on angiographic images. CASE PRESENTATION: A 58-year-old female patient with intermittent chest pain for 5 years and polycythaemia vera (PV) for 8 years. The left anterior descending artery was presented like WCA on coronary angiography and finally confirmed as recanalized thrombus by optical coherence tomography(OCT), which might have been caused by PV. Given the patient's high thrombotic risk of PV and thrombotic changes in the left circumflex artery (LCX), we ultimately chose a conservative treatment without stenting. CONCLUSIONS: OCT would be needed for the diagnosis and differential diagnosis of woven-like coronary arteries. And physicians should take an appropriate treatment in a personalized way in patients with PV.

Diffuse pulmonary arteriovenous malformation presenting with secondary polycythemia and headaches: a case report.

BACKGROUND: Pulmonary arteriovenous malformations are a relatively uncommon medical condition, affecting roughly 1 in every 2500 individuals. Of those suffering from pulmonary arteriovenous malformations, 80% have an underlying genetic condition: hereditary hemorrhagic telangiectasia. CASE PRESENTATION: We present the case of a 20-year-old Pakistani male with a history of persistent slower-onset frontal headaches that increased in severity within the course of the day. His hemoglobin was 18 g/dl, indicating polycythemia, for which he had undergone seven venesections in a month previously. His physical examination was unremarkable. His computed tomography scan depicted multiple dilated tortuous vessels with branching linear opacities in the right lower lobe of the lungs. The multiple feeding arteries were supplied by the right main pulmonary artery, and the large draining veins led to the right inferior pulmonary vein. This was identified as a diffuse pulmonary arteriovenous malformation. He was recommended for a right pulmonary artery angiogram. It showed multiple tortuous vessels with a nidus and large draining veins-features of a diffuse arteriovenous malformation in the right lower lobe of the lung consistent with the computed tomography scan. Embolization of two of these vessels feeding the arteriovenous malformation was conducted, using Amplatzer Vascular plug 2, whereas multiple pushable coils (five coils) were used for embolizing the third feeding vessel. This achieved 70-80% successful embolization of right pulmonary AVM; however, some residual flow was still seen in the arteriovenous malformation given the complexity of the lesion. Immediately after, his oxygen saturation improved from 78% to 96%. CONCLUSION: Diffuse pulmonary arteriovenous malformations, as seen in this patient, are rare, accounting for less than 5% of total pulmonary arteriovenous malformations diagnosed. The patient presented with a complaint of progressive frontal headaches, which can be attributed to low oxygen saturation or the presence of a cerebral arteriovenous malformation. There was no history of hereditary hemorrhagic telangiectasia in the patient's family. Furthermore, although most patients with hereditary hemorrhagic telangiectasia and hence pulmonary arteriovenous malformation have complaints of iron-deficiency anemia, our patient in contrast was suffering from polycythemia. This can be explained as a compensatory mechanism in hypoxemic conditions. Moreover, the patient had no complaint of hemoptysis or epistaxis, giving a varied presentation in comparison with a typical pulmonary arteriovenous malformation.

Advancements and Future Directions in Polycythemia Vera Research: A Bibliometric Analysis.

This research provides a comprehensive bibliometric analysis of polycythemia vera (PV) research trends, encompassing data from 1969 to 2024. Utilizing advanced tools, key findings reveal a notable increase in scientific production over time, reflecting growing interest and investment in PV research. Prominent themes include genetic studies, targeted therapies, and precision medicine approaches. The analysis identifies leading authors, institutions, and countries contributing to PV research, highlighting the importance of global collaboration. The study emphasizes the need to broaden genetic investigations, explore the bone marrow microenvironment, and enhance precision medicine strategies. The implications of this research extend to clinical practice, with potential advancements in diagnostics, treatments, and patient outcomes. Ultimately, addressing these challenges and embracing emerging opportunities can propel PV research forward, fostering innovation and improving the lives of affected individuals.

Relationship between amide ratio assessed by Fourier-transform infrared spectroscopy: A biomarker candidate for polycythemia vera disease.

The study utilized Fourier transform infrared (FTIR) spectroscopy coupled with chemometrics to investigate protein composition and structural changes in the blood serum of patients with polycythemia vera (PV). Principal component analysis (PCA) revealed distinct biochemical properties, highlighting elevated absorbance of phospholipids, amides, and lipids in PV patients compared to healthy controls. Ratios of amide I/amide II and amide I/amide III indicated alterations in protein structures. Support vector machine analysis and receiver operating characteristic curves identified amide I as a crucial predictor of PV, achieving 100% accuracy, sensitivity, and specificity, while amide III showed a lower predictive value (70%). PCA analysis demonstrated effective differentiation between PV patients and controls, with key wavenumbers including amide II, amide I, and CH lipid vibrations. These findings underscore the potential of FTIR spectroscopy for diagnosing and monitoring PV.

Efficacy and safety outcomes in Japanese patients with low-risk polycythemia vera treated with ropeginterferon alfa-2b.

Polycythemia vera (PV) is a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by clonal erythrocytosis. A phase 2 study reported that ropeginterferon alfa-2b is a well-tolerated and effective treatment for PV in Japanese patients. This post hoc analysis of the phase 2 data further evaluated outcomes in patients at low risk of thrombosis (low-risk PV). Among 20 patients with low-risk PV, 60.0% (12/20) and 85.0% (17/20) achieved < 45% hematocrit by weeks 24 and 52, respectively. The proportion of responders with complete hematologic response (CHR) was 60.0% (12/20) at week 52, and the median time to response was 11.9 months. The mean JAK2 V617F allele burden decreased from 75.8% at baseline to 53.7% at week 52. No patient experienced thrombosis or bleeding episodes. All patients experienced treatment-emergent adverse events (TEAEs) related to ropeginterferon alfa-2b, but no grade ≥ 3 TEAEs or deaths related to ropeginterferon alfa-2b occurred, and no new safety concerns arose. This analysis indicated that ropeginterferon alfa-2b may be an effective treatment option for Japanese patients with low-risk PV.

Spinal extramedullary hematopoiesis mimicking an epidural tumor in a patient with high-risk polycythemia vera: illustrative case.

BACKGROUND: Here the authors present the case of a 43-year-old male with a history of T-cell lymphoma, which was treated with azacitidine plus cyclophosphamide, doxorubicin, vincristine, and prednisone and autologous hematopoietic cell transplant, and high-risk polycythemia vera (PCV) presenting with severe lower-back pain radiating to the bilateral legs with associated lower-extremity weakness and splenomegaly. OBSERVATIONS: T2-weighted magnetic resonance imaging revealed multilevel epidural lesions involving T1-10 and S1-2. Because of severe spinal canal stenosis, the patient underwent surgical decompression of T5-7, with immediate postoperative alleviation of the lower-extremity pain and complete resolution of the lower-leg weakness. Biopsy results revealed extramedullary hematopoiesis (EMH) mimicking a spinal epidural tumor. EMH is radiosensitive and displays a rapid response to low dosages, so the patient was further treated with palliative radiation therapy for residual tumors and symptom alleviation, as well as hydroxyurea and corticosteroids as indicated for cytoreduction. LESSONS: EMH associated with PCV or myeloproliferative conditions occurring within the spine is a rare phenomenon without a standard treatment approach. https://thejns.org/doi/10.3171/CASE23659.